Global Patent Index - EP 1158045 A1

EP 1158045 A1 20011128 - Culture conditions allowing to modulate the expression of CYP3A4 in CaCo2 cells

Title (en)

Culture conditions allowing to modulate the expression of CYP3A4 in CaCo2 cells

Title (de)

Kulturzustände die erlauben die Modulierung der Expression von CYP3A4 in CaCo2 Zellen

Title (fr)

Conditions de culture permettant de moduler l'expression de CYP3A4 dans des cellules CaCo2

Publication

EP 1158045 A1 20011128 (EN)

Application

EP 00870108 A 20000517

Priority

EP 00870108 A 20000517

Abstract (en)

The present invention relates to the field of the expression of biotransformation activities in cell culture systems. The present invention discloses basal and well defined culture conditions for CaCo 2 cells and therefore provide for in vitro model systems of the intestinal barrier as a tool in pharmaco-toxicology. In these model systems are most, if not all, biotransformation activities expressed in vitro, present, providing a model mimicking the in vivo reality. Under the culture conditions disclosed by the present invention, the expression of these activities, and especially the expression of CYP3A4, does not rely upon the addition of any inducer for CYP3A4 expression. These culture conditions further comprise the use of permeable culture inserts containing either a polyethylene terephtalate (PET) or an Anopore TM membrane. Furthermore, the present invention discloses CaCo 2 cell lines which show an enhanced expression of CYP3A4 in comparison with their parental cell lines, when grown without the addition of an inducer for CYP3A4 expression.

IPC 1-7

C12N 5/08; G01N 33/50

IPC 8 full level

C12N 5/09 (2010.01)

CPC (source: EP)

C12N 5/0679 (2013.01); C12N 5/0693 (2013.01); C12N 2501/11 (2013.01); C12N 2501/33 (2013.01); C12N 2501/39 (2013.01); C12N 2503/02 (2013.01)

Citation (search report)

  • [A] US 5856189 A 19990105 - WATKINS PAUL B [US], et al
  • [X] FISHER JEANNINE M ET AL: "Midazolam metabolism by modified Caco-2 monolayers: Effects of extracellular protein binding.", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 289, no. 2, May 1999 (1999-05-01), pages 1143 - 1150, XP000982476, ISSN: 0022-3565
  • [A] SCHUETZ ERIN G ET AL: "Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.", MOLECULAR PHARMACOLOGY, vol. 49, no. 2, 1996, pages 311 - 318, XP000906895, ISSN: 0026-895X
  • [DA] SCHMKIEDLIN-REN PHYLLSSA ET AL: "Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1-alpha,25-dihydroxyvitamin D-3.", MOLECULAR PHARMACOLOGY, vol. 51, no. 5, 1997, pages 741 - 754, XP002161257, ISSN: 0026-895X

Designated contracting state (EPC)

AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

DOCDB simple family (publication)

EP 1158045 A1 20011128

DOCDB simple family (application)

EP 00870108 A 20000517